The long term objective of this research is to diagnose cancer via a blood test at an earlier stage and thereby increase the cure rate. We will focus in this program on developing our two instruments to follow genetic changes associated with progressive carcinoma and thereby, eventually help to personalize therapy. It is known that malignant solid tumors shed tumor cells into the circulation at a relatively early stage in their growth. Therefore, if it were possible to capture these relatively rare cells (CTCs) and prove that they are malignant, earlier diagnosis would be expected. Microchips that capture CTCs with great sensitivity have been recently described. We have made such a microchip with proven sensitivity but have altered it using immunolablled nanomagnetic particles for capturing CTCs, which can then be released to an innovative hyperspectral imaging microscope (HMI) that can precisely quantify 10 tumor markers (TMs) in a single pass. The proposed CTC chip-HMI platform can find tumor markers in blood in less than an hour, and with 10-fold greater sensitivity and specificity then existing (commercial) devices such as Cell Tracks, an FDA approved instrument for determining prognosis and treatment effectiveness in breast cancer based on a very small number of captured CTCs. A major breakthrough is the demonstration that over expression of TMs by cancer breast cells allows them to be distinguished from normal breast cells which have consistently less over expression of TMs. Therefore, after capture of the CTCs, evaluation of their TM expression by the HMI and the pathologist's conclusion concerning malignancy, we can then allow for the development of criteria for the number and extent of TM over expression that minimizes false positives but not at the expense of increasing false negatives. The extent and patterns of over expression of particular TMs will also be of considerable value for prognosis and treatment decisions. We will study breast carcinoma as a prototype of other carcinomas, primarily due to that the malignant tumors can be precisely measured radiographically and we have a large supply of patients. We plan to focus on the ability of our instrumentation to find CTCs in patients with small breast carcinomas.